Abstract
The methylxanthine derivative pentoxifylline (PTX) is an immunomodulatory agent with incompletely characterized effects on cytokine production. To analyse these effects and to delineate new combination strategies in immunotherapy, we have investigated immunomodulatory properties of PTX in combination with dexamethasone (DEX) or cyclosporin A (CsA). Stimulated human peripheral blood mononuclear cells were treated with clinically relevant concentrations of PTX (12.5-100 micrograms/ml), DEX (0.01-10 microM) or CsA (12.5-50 ng/ml), alone or in combination. With increasing doses of PTX the maximum supernatant titres of tumour necrosis factor (TNF)-alpha, interleukin (IL)-2 and interferon (IFN)-gamma decreased concomitantly, and all cultures co-treated with DEX showed synergism. Release of IL-6 was not consistently altered under PTX treatment. Similarly, PTX and CsA synergistically inhibited the release of IL-2, IFN-gamma and, to a lesser degree, TNF-alpha. Although PTX alone did not significantly reduce lymphoproliferation, both combinations of drugs synergistically inhibited this process. Furthermore, to demonstrate that the key mechanism of PTX-induced effects is an increase in intracellular cyclic adenosine 3':5'-monophosphate (c...Continue Reading
References
Apr 1, 1992·Immunology Today·S L Schreiber, G R Crabtree
Nov 1, 1992·Immunopharmacology·L A RosenthalK J Blank
Oct 1, 1992·The Journal of Infectious Diseases·C C ChaoP K Peterson
Jun 15, 1991·Thrombosis Research·S OhdamaN Aoki
Jan 18, 1991·Science·S L Schreiber
Jul 1, 1991·Cellular Immunology·K M RaoH J Cohen
Oct 1, 1991·Immunology Today·R P PhippsR L Roper
Mar 3, 1990·Lancet·A WaageB Størdal
Apr 1, 1991·Transplantation·J A BiancoJ W Singer
Jul 1, 1990·The Journal of Experimental Medicine·J HanB Beutler
Sep 30, 1988·Biochemical and Biophysical Research Communications·R M StrieterS L Kunkel
May 12, 1989·Journal of Immunological Methods·M B HansenK Berg
Jan 1, 1989·Renal Failure·L J BrunnerD R Luke
May 1, 1989·Cellular Immunology·S M TaffetS A Shurtleff
Dec 23, 1989·Lancet·P ZabelU F Schade
Feb 10, 1989·Cell·M Beato
Jan 1, 1988·Journal of Steroid Biochemistry·P M GuyreP D Manganiello
Oct 1, 1987·European Journal of Immunology·L A AardenP M Lansdorp
Dec 4, 1986·Journal of Immunological Methods·T Espevik, J Nissen-Meyer
Aug 1, 1993·Immunology Letters·K RieneckK Bendtzen
Aug 1, 1994·European Journal of Immunology·N ReilingS Hauschildt
Jan 1, 1993·Cancer Immunology, Immunotherapy : CII·B J DezubeA B Pardee
Jan 1, 1995·European Journal of Immunology·B SinhaS Endres
Mar 1, 1994·International Immunology·E M EuguiA C Allison
Apr 1, 1993·Immunobiology·P ZabelM Schlaak
Jul 1, 1993·Transplantation·H TilgD Niederwieser
Mar 1, 1993·Immunopharmacology·L A Rosenthal, K J Blank
Jun 1, 1993·The Journal of Experimental Medicine·A L MoreiraG Kaplan
Citations
Jul 3, 1998·Journal of Clinical Pharmacology·W A BriggsJ Burdick
Sep 16, 2010·Clinical Rheumatology·Iliana AlexoudiGeorge Vaiopoulos
Oct 5, 2001·Atherosclerosis·T M LeeS S Wang
Nov 1, 1996·International Journal of Immunopharmacology·D W HoskinA P Makrigiannis
Dec 1, 1996·International Journal of Immunopharmacology·C L D'HellencourtM Guenounou
Sep 8, 1998·International Journal of Immunopharmacology·M Richard, D W Hoskin
Aug 1, 1997·General Pharmacology·C Windmeier, A M Gressner
Mar 26, 2003·Journal of Gastroenterology and Hepatology·Orhan TarçinAhmet K Gürbüz
Jan 7, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M WördemannW Jelkmann
Mar 10, 2012·Neurology·D M EscolarJ K Mah
Mar 21, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jin-Moo LeeJan Xu
Apr 30, 1998·Infection·A DhondtS Ringoir
Apr 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·A SinghM J Reed
Dec 21, 2006·International Immunopharmacology·Zorica Stojić VukanićM Dimitrijević
May 30, 2006·Pharmacology & Therapeutics·Waldiceu A VerriSérgio H Ferreira
Jan 1, 2005·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Jan OsterreicherYvona Mazurová
Jul 4, 2001·The American Journal of Cardiology·D L Dawson
Jun 9, 1998·Respiratory Medicine·J Müller-Quernheim
Jan 13, 2018·International Journal of Molecular Sciences·Grzegorz WystrychowskiAntoni Wystrychowski
May 2, 2018·PloS One·Esther M SpeerOfer Levy
Apr 25, 2003·Vascular Medicine·Steven M Dean
Dec 17, 2009·Expert Opinion on Therapeutic Targets·Sabina A Antoniu
Aug 29, 1998·Allergy·P EntzianP Zabel
Oct 18, 2019·Veterinary Medicine and Science·Evangel KummariTodd Archer